US 12,247,045 B2
MAP4K4 inhibitors
Michael Schneider, London (GB); Gary Newton, Saffron Walden (GB); Kathryn Chapman, Saffron Walden (GB); Ashley Jarvis, Abingdon (GB); Rehan Aqil, Saffron Walden (GB); Tifelle Reisinger, Saffron Walden (GB); Melanie Bayford, Saffron Walden (GB); Nicholas Chapman, Saffron Walden (GB); Nicholas Martin, Saffron Walden (GB); and David Middlemiss, Heartfordshire (GB)
Assigned to Imperial College Innovations Limited, London (GB)
Appl. No. 17/298,870
Filed by Imperial College Innovations Limited, London (GB)
PCT Filed Dec. 4, 2019, PCT No. PCT/GB2019/053429
§ 371(c)(1), (2) Date Jun. 1, 2021,
PCT Pub. No. WO2020/115481, PCT Pub. Date Jun. 11, 2020.
Claims priority of application No. 1819839 (GB), filed on Dec. 5, 2018.
Prior Publication US 2023/0055250 A1, Feb. 23, 2023
Int. Cl. C07F 9/6561 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01)
CPC C07F 9/6561 (2013.01) [C07D 471/04 (2013.01); C07D 487/04 (2013.01)] 30 Claims
OG exemplary drawing
 
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof, or a compound selected from List A, or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein
W is independently selected from N or C;
Z is independently selected from H or —CH2OP(═O)(OH)2;
either X is N and Y is C, or Y is N and X is C;
ring A is independently selected from an aryl and a 5 to 10 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O and S;
ring B is independently selected from an aryl and a 5 or 6 membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O and S;
provided that ring A and ring B of the compound of formula (I) are not both phenyl;
L1 and L3 are independently selected from a bond, —(CRaRb)m—, —O(CRaRb)m— or —NH(CRaRb)m—, wherein m is at each occurrence independently selected from 1, 2, 3, or 4;
Z1 is a bond, —NR5a—, —O—, —C(O)—, —SO2—, —SO2NR5a—, —NR5aSO2—, —C(O)NR5a—, —NR5aC(O)—, —C(O)O—, or —NR5aC(O)NR5a—;
Z2 is a bond, —NR5b—, —O—, —C(O)—, —SO2—, —SO2NR5a—, —NR5aSO2—, —C(O)NR5a—, —NR5bC(O)—, or —C(O)O—;
L2 and L4 are independently either a bond or —(CRcRd)n—, wherein n is at each occurrence independently selected from 1, 2, 3, or 4;
R1 is selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C1-6 haloalkyl, —NR6aR6b, —OR6a, OP(═O)(OH)2, —C(O)R6a, 5 or 6 membered heteroaryl rings, or 3 to 8 membered heterocycloalkyl ring systems,
wherein the heteroaryl and heterocycloalkyl rings are unsubstituted or substituted with 1 or 2 groups selected from: C1-6 alkyl, oxo, halo, OR6a, C1-6 alkyl, C1-6 alkyl substituted with NR6aR6b, C1-6 alkyl substituted with OR6a, —C(O)R7, and —NR8(O)R7;
R2 is selected from halo, C1-6 alkyl, C2-6 alkenyl, C1-6 haloalkyl, —NR6aR6b, —OR6a OP(═O)(OH)2, —C(O)R6a, —NR5bC(O)O—C1-6 alkyl, phenyl, 5 or 6 membered heteroaryl rings, 3 to 8 membered cycloalkyl rings, or 3 to 8 membered heterocycloalkyl ring systems,
wherein the phenyl, heteroaryl, cycloalkyl and heterocycloalkyl rings are unsubstituted or substituted with 1 or 2 groups selected from: oxo, halo, OR6a, C1-6 alkyl, C1-6 alkyl substituted with NR6aR6b, C1-6 alkyl substituted with OR6a, C(O)R6a, —C(O)ORg, and —NR8C(O)R7;
R3 and R4 are independently selected from H, halo, —CN and C1-6 alkyl;
R5a and R5b are independently selected at each occurrence, from: H, C1-6 alkyl, or C3-6 cycloalkyl;
R6a and R6b are, independently selected at each occurrence, from: H, C1-6 alkyl, C1-6 alkyl substituted with −ORe, C1-6 alkyl substituted with —NReRf, and C3-6 cycloalkyl;
R7 is selected from H, —OR8, C1-6 alkyl and C3-6 cycloalkyl;
R8 is selected from H and C1-6 alkyl;
Ra, Rb, Rc and Rd are, at each occurrence, independently selected from: H, halo, C1-6 alkyl, and —ORh, or Ra and Rb or Rc and Rd taken together with the atom to which they are attached form a 3 to 6 membered cycloalkyl ring or a 3 to 6 membered heterocycloalkyl ring containing 1 or 2 O, N or S atoms, wherein the cycloalkyl ring is unsubstituted or substituted with 1 or 2 halo groups; and
Re, Rf, Rg and Rh are each independently selected at each occurrence from H or C1-6 alkyl;
and wherein List A is a compound selected from the group consisting of:

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